The long-term objective of this project is to discover the regulatory mechanisms which maintain constancy of the electrolyte content of excitable cells. The current emphasis is on the regulatory mechanisms active in maintaining constancy of the internal levels of the divalent cations calcium and magnesium. The specific aims of the current project are centered on an investigation of how potassium and sodium ions interrelate in the activation of a Mg ion pump that uses energy either from ATP directly or from K and Na electrochemical gradients to extrude Mg ions out of the cell against a thermodynamic gradient for Mg. It has been found in previous work on this project that one component of Mg ion extrusion from barnacle giant muscle fibers is activated by potassium ions in the external medium. The mechanism for this activation is unknown and the project seeks to explain the mechanism by which K ions activate Mg ion extrusion. One possibility is that a K/Mg counter transport system is present. Another possibility is the presence of an ATP-driven Mg pump using a transport ATPase and ATP hydrolysis to outwardly transport Mg ions. It is possible that such an ATP-driven pump is at least partially activated by external K ions and that the presence of external K ions is a requirement for Mg pump activity. The project also seeks to learn the stoichiometry of any coupling that might be present between K ion movement and Mg ion movement. Intracellular Mg ions are required for the activity of several intracellular enzymes. In relating Mg ions to possible relevant areas of disease, Mg is important in regulating the excitability of nerve and muscle and is also involved in the generation of cardiac arrhythmias. Similarities in the handling of K and Mg ions by cells are known and this investigation seeks to further explore the basis for such similarities.